{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T19:29:45Z","timestamp":1778786985386,"version":"3.51.4"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T00:00:00Z","timestamp":1592870400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T00:00:00Z","timestamp":1592870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 104-2627-B-002-001, MOST 106-2320-B-002-053-MY3"],"award-info":[{"award-number":["MOST 104-2627-B-002-001, MOST 106-2320-B-002-053-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST107-2221-E-010-017-MY2"],"award-info":[{"award-number":["MOST107-2221-E-010-017-MY2"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 108-2321-B-006-002"],"award-info":[{"award-number":["MOST 108-2321-B-006-002"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Biomed Sci"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>ZNF322A is an oncogenic transcription factor that belongs to the Cys2His2-type zinc-finger protein family. Accumulating evidence suggests that ZNF322A may contribute to the tumorigenesis of lung cancer, however, the ZNF322A-mediated downstream signaling pathways remain unknown.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>To uncover ZNF322A-mediated functional network, we applied phosphopeptide enrichment and isobaric labeling strategies with mass spectrometry-based proteomics using A549 lung cancer cells, and analyzed the differentially expressed proteins of phosphoproteomic and proteomic profiles to determine ZNF322A-modulated pathways.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>ZNF322A highlighted a previously unidentified insulin signaling, heat stress, and signal attenuation at the post-translational level. Consistently, protein-phosphoprotein-kinase interaction network analysis revealed phosphorylation of IRS1 and HSP27 were altered upon ZNF322A-silenced lung cancer cells. Thus, we further investigated the molecular regulation of ZNF322A, and found the inhibitory transcriptional regulation of ZNF322A on PIM3, which was able to phosphorylate IRS1 at serine<jats:sup>1101<\/jats:sup> in order to manipulate glucose uptake via the PI3K\/AKT\/mTOR signaling pathway. Moreover, ZNF322A also affects the unfolded protein response by phosphorylation of HSP27<jats:sup>S82<\/jats:sup> and eIF2a<jats:sup>S51<\/jats:sup>, and triggers autophagosome formation in lung cancer cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These findings not only give new information about the molecular regulation of the cellular proteins through ZNF322A at the post-translational level, but also provides a resource for the study of lung cancer therapy.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12929-020-00668-5","type":"journal-article","created":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T04:14:48Z","timestamp":1592885688000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["ZNF322A-mediated protein phosphorylation induces autophagosome formation through modulation of IRS1-AKT glucose uptake and HSP-elicited UPR in lung cancer"],"prefix":"10.1186","volume":"27","author":[{"given":"Chantal Hoi Yin","family":"Cheung","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Lang","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsai-Yu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Ting","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ching","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsuan-Cheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4876-3309","authenticated-orcid":false,"given":"Hsueh-Fen","family":"Juan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,6,23]]},"reference":[{"key":"668_CR1","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1146\/annurev.biophys.29.1.183","volume":"29","author":"SA Wolfe","year":"2000","unstructured":"Wolfe SA, Nekludova L, Pabo CO. DNA recognition by Cys2His2 zinc finger proteins. Annu Rev Biophys Biomol Struct. 2000;29:183\u2013212.","journal-title":"Annu Rev Biophys Biomol Struct"},{"issue":"5","key":"668_CR2","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/ncb1864","volume":"11","author":"C Tian","year":"2009","unstructured":"Tian C, Xing G, Xie P, Lu K, Nie J, Wang J, et al. KRAB-type zinc-finger protein Apak specifically regulates p53-dependent apoptosis. Nat Cell Biol. 2009;11(5):580\u201391.","journal-title":"Nat Cell Biol"},{"issue":"21","key":"668_CR3","doi-asserted-by":"publisher","first-page":"18282","DOI":"10.1074\/jbc.M010885200","volume":"276","author":"AH Jheon","year":"2001","unstructured":"Jheon AH, Ganss B, Cheifetz S, Sodek J. Characterization of a novel KRAB\/C2H2 zinc finger transcription factor involved in bone development. J Biol Chem. 2001;276(21):18282\u20139.","journal-title":"J Biol Chem"},{"issue":"21","key":"668_CR4","doi-asserted-by":"publisher","first-page":"15685","DOI":"10.1074\/jbc.M910152199","volume":"275","author":"S Wagner","year":"2000","unstructured":"Wagner S, Hess MA, Ormonde-Hanson P, Malandro J, Hu H, Chen M, et al. A broad role for the zinc finger protein ZNF202 in human lipid metabolism. J Biol Chem. 2000;275(21):15685\u201390.","journal-title":"J Biol Chem"},{"issue":"1","key":"668_CR5","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.molcel.2013.01.024","volume":"50","author":"S Chauhan","year":"2013","unstructured":"Chauhan S, Goodwin JG, Chauhan S, Manyam G, Wang J, Kamat AM, et al. ZKSCAN3 is a master transcriptional repressor of autophagy. Mol Cell. 2013;50(1):16\u201328.","journal-title":"Mol Cell"},{"issue":"30","key":"668_CR6","doi-asserted-by":"publisher","first-page":"26516","DOI":"10.1074\/jbc.M110.212506","volume":"286","author":"S Meruvu","year":"2011","unstructured":"Meruvu S, Hugendubler L, Mueller E. Regulation of adipocyte differentiation by the zinc finger protein ZNF638. J Biol Chem. 2011;286(30):26516\u201323.","journal-title":"J Biol Chem"},{"issue":"18","key":"668_CR7","doi-asserted-by":"publisher","first-page":"2357","DOI":"10.1038\/onc.2015.296","volume":"35","author":"J Jen","year":"2016","unstructured":"Jen J, Lin LL, Chen HT, Liao SY, Lo FY, Tang YA, et al. Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin, cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer. Oncogene. 2016;35(18):2357\u201369.","journal-title":"Oncogene."},{"issue":"41","key":"668_CR8","doi-asserted-by":"publisher","first-page":"5722","DOI":"10.1038\/onc.2017.168","volume":"36","author":"SY Liao","year":"2017","unstructured":"Liao SY, Chiang CW, Hsu CH, Chen YT, Jen J, Juan HF, et al. CK1delta\/GSK3beta\/FBXW7alpha axis promotes degradation of the ZNF322A oncoprotein to suppress lung cancer progression. Oncogene. 2017;36(41):5722\u201333.","journal-title":"Oncogene."},{"issue":"7","key":"668_CR9","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1038\/s41418-018-0204-6","volume":"26","author":"J Jen","year":"2019","unstructured":"Jen J, Liu CY, Chen YT, Wu LT, Shieh YC, Lai WW, et al. Oncogenic zinc finger protein ZNF322A promotes stem cell-like properties in lung cancer through transcriptional suppression of c-Myc expression. Cell Death Differ. 2019;26(7):1283\u201398.","journal-title":"Cell Death Differ"},{"key":"668_CR10","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1186\/1471-2407-12-235","volume":"12","author":"FY Lo","year":"2012","unstructured":"Lo FY, Chang JW, Chang IS, Chen YJ, Hsu HS, Huang SF, et al. The database of chromosome imbalance regions and genes resided in lung cancer from Asian and Caucasian identified by array-comparative genomic hybridization. BMC Cancer. 2012;12:235.","journal-title":"BMC Cancer"},{"issue":"8","key":"668_CR11","first-page":"3319","volume":"6","author":"GW Krystal","year":"2000","unstructured":"Krystal GW, Honsawek S, Litz J, Buchdunger E. The selective tyrosine kinase inhibitor STI571 inhibits small cell lung cancer growth. Clin Cancer Res. 2000;6(8):3319\u201326.","journal-title":"Clin Cancer Res"},{"key":"668_CR12","doi-asserted-by":"publisher","first-page":"2651","DOI":"10.1038\/srep02651","volume":"3","author":"J Reimand","year":"2013","unstructured":"Reimand J, Wagih O, Bader GD. The mutational landscape of phosphorylation signaling in cancer. Sci Rep. 2013;3:2651.","journal-title":"Sci Rep"},{"issue":"22","key":"668_CR13","doi-asserted-by":"publisher","first-page":"3279","DOI":"10.1038\/sj.onc.1210421","volume":"26","author":"AS Dhillon","year":"2007","unstructured":"Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene. 2007;26(22):3279\u201390.","journal-title":"Oncogene."},{"issue":"12","key":"668_CR14","doi-asserted-by":"publisher","first-page":"3127","DOI":"10.1002\/cncr.10591","volume":"94","author":"N Itoh","year":"2002","unstructured":"Itoh N, Semba S, Ito M, Takeda H, Kawata S, Yamakawa M. Phosphorylation of Akt\/PKB is required for suppression of cancer cell apoptosis and tumor progression in human colorectal carcinoma. Cancer. 2002;94(12):3127\u201334.","journal-title":"Cancer."},{"key":"668_CR15","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1146\/annurev.pharmtox.011008.145606","volume":"49","author":"B Macek","year":"2009","unstructured":"Macek B, Mann M, Olsen JV. Global and site-specific quantitative phosphoproteomics: principles and applications. Annu Rev Pharmacol Toxicol. 2009;49:199\u2013221.","journal-title":"Annu Rev Pharmacol Toxicol"},{"issue":"9","key":"668_CR16","doi-asserted-by":"publisher","first-page":"3163","DOI":"10.1158\/1078-0432.CCR-04-2243","volume":"11","author":"YP Lim","year":"2005","unstructured":"Lim YP. Mining the tumor phosphoproteome for cancer markers. Clin Cancer Res. 2005;11(9):3163\u20139.","journal-title":"Clin Cancer Res"},{"issue":"6","key":"668_CR17","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/j.molonc.2010.09.004","volume":"4","author":"HC Harsha","year":"2010","unstructured":"Harsha HC, Pandey A. Phosphoproteomics in cancer. Mol Oncol. 2010;4(6):482\u201395.","journal-title":"Mol Oncol"},{"issue":"2","key":"668_CR18","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.cell.2012.03.017","volume":"149","author":"M Laplante","year":"2012","unstructured":"Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012;149(2):274\u201393.","journal-title":"Cell."},{"issue":"11","key":"668_CR19","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.7150\/ijbs.27173","volume":"14","author":"X Huang","year":"2018","unstructured":"Huang X, Liu G, Guo J, Su Z. The PI3K\/AKT pathway in obesity and type 2 diabetes. Int J Biol Sci. 2018;14(11):1483\u201396.","journal-title":"Int J Biol Sci"},{"issue":"6","key":"668_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.299","volume":"8","author":"C Geronimo-Olvera","year":"2017","unstructured":"Geronimo-Olvera C, Montiel T, Rincon-Heredia R, Castro-Obregon S, Massieu L. Autophagy fails to prevent glucose deprivation\/glucose reintroduction-induced neuronal death due to calpain-mediated lysosomal dysfunction in cortical neurons. Cell Death Dis. 2017;8(6):e2911.","journal-title":"Cell Death Dis"},{"issue":"6","key":"668_CR21","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1038\/sj.onc.1208095","volume":"24","author":"T Kanzawa","year":"2005","unstructured":"Kanzawa T, Zhang L, Xiao L, Germano IM, Kondo Y, Kondo S. Arsenic trioxide induces autophagic cell death in malignant glioma cells by upregulation of mitochondrial cell death protein BNIP3. Oncogene. 2005;24(6):980\u201391.","journal-title":"Oncogene."},{"issue":"52","key":"668_CR22","doi-asserted-by":"publisher","first-page":"18030","DOI":"10.1073\/pnas.0408345102","volume":"101","author":"Y Shao","year":"2004","unstructured":"Shao Y, Gao Z, Marks PA, Jiang X. Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. Proc Natl Acad Sci. 2004;101(52):18030\u2013180305.","journal-title":"Proc Natl Acad Sci"},{"issue":"1","key":"668_CR23","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.pharmthera.2011.03.009","volume":"131","author":"JM Levy","year":"2011","unstructured":"Levy JM, Thorburn A. Targeting autophagy during cancer therapy to improve clinical outcomes. Pharmacol Ther. 2011;131(1):130\u201341.","journal-title":"Pharmacol Ther"},{"issue":"6","key":"668_CR24","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/nrm1666","volume":"6","author":"EH Baehrecke","year":"2005","unstructured":"Baehrecke EH. Autophagy: dual roles in life and death? Nat Rev Mol Cell Biol. 2005;6(6):505\u201310.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"3","key":"668_CR25","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.bcp.2014.05.011","volume":"90","author":"C Fumarola","year":"2014","unstructured":"Fumarola C, Bonelli MA, Petronini PG, Alfieri RR. Targeting PI3K\/AKT\/mTOR pathway in non small cell lung cancer. Biochem Pharmacol. 2014;90(3):197\u2013207.","journal-title":"Biochem Pharmacol"},{"issue":"2","key":"668_CR26","doi-asserted-by":"publisher","first-page":"430","DOI":"10.3892\/or.2012.2131","volume":"29","author":"M Chen","year":"2013","unstructured":"Chen M, Du Y, Qui M, Wang M, Chen K, Huang Z, et al. Ophiopogonin B-induced autophagy in non-small cell lung cancer cells via inhibition of the PI3K\/Akt signaling pathway. Oncol Rep. 2013;29(2):430\u20136.","journal-title":"Oncol Rep"},{"issue":"8","key":"668_CR27","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1038\/nprot.2007.261","volume":"2","author":"J Rappsilber","year":"2007","unstructured":"Rappsilber J, Mann M, Ishihama Y. Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips. Nat Protoc. 2007;2(8):1896\u2013906.","journal-title":"Nat Protoc"},{"issue":"1","key":"668_CR28","doi-asserted-by":"publisher","first-page":"13302","DOI":"10.1038\/s41598-017-13440-x","volume":"7","author":"CHY Cheung","year":"2017","unstructured":"Cheung CHY, Hsu CL, Chen KP, Chong ST, Wu CH, Huang HC, et al. MCM2-regulated functional networks in lung cancer by multi-dimensional proteomic approach. Sci Rep. 2017;7(1):13302.","journal-title":"Sci Rep"},{"issue":"5","key":"668_CR29","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1074\/mcp.RA117.000530","volume":"17","author":"S Liu","year":"2018","unstructured":"Liu S, Yu F, Yang Z, Wang T, Xiong H, Chang C, et al. Establishment of dimethyl labeling-based quantitative Acetylproteomics in Arabidopsis. Mol Cell Proteomics. 2018;17(5):1010\u201327.","journal-title":"Mol Cell Proteomics"},{"issue":"11","key":"668_CR30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013984","volume":"5","author":"D Merico","year":"2010","unstructured":"Merico D, Isserlin R, Stueker O, Emili A, Bader GD. Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS One. 2010;5(11):e13984.","journal-title":"PLoS One"},{"key":"668_CR31","doi-asserted-by":"crossref","unstructured":"Hsu CL, Wang JK, Lu PC, Huang HC, Juan HF. DynaPho: a web platform for inferring the dynamics of time-series phosphoproteomics. Bioinformatics. 2017.","DOI":"10.1093\/bioinformatics\/btx443"},{"issue":"2","key":"668_CR32","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ccr.2012.12.007","volume":"23","author":"C Sourbier","year":"2013","unstructured":"Sourbier C, Scroggins BT, Ratnayake R, Prince TL, Lee S, Lee MJ, et al. Englerin a stimulates PKCtheta to inhibit insulin signaling and to simultaneously activate HSF1: pharmacologically induced synthetic lethality. Cancer Cell. 2013;23(2):228\u201337.","journal-title":"Cancer Cell"},{"issue":"8","key":"668_CR33","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1111\/j.1600-0854.2009.00938.x","volume":"10","author":"N Hamilton","year":"2009","unstructured":"Hamilton N. Quantification and its applications in fluorescent microscopy imaging. Traffic. 2009;10(8):951\u201361.","journal-title":"Traffic."},{"issue":"4","key":"668_CR34","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/ilar.43.4.207","volume":"43","author":"RB Dell","year":"2002","unstructured":"Dell RB, Holleran S, Ramakrishnan R. Sample size determination. ILAR J. 2002;43(4):207\u201313.","journal-title":"ILAR J"},{"issue":"15","key":"668_CR35","doi-asserted-by":"publisher","first-page":"20152","DOI":"10.18632\/oncotarget.7918","volume":"7","author":"JH Song","year":"2016","unstructured":"Song JH, Padi SK, Luevano LA, Minden MD, DeAngelo DJ, Hardiman G, et al. Insulin receptor substrate 1 is a substrate of the Pim protein kinases. Oncotarget. 2016;7(15):20152\u201365.","journal-title":"Oncotarget."},{"issue":"11","key":"668_CR36","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.4161\/cc.10.11.15824","volume":"10","author":"LM Shaw","year":"2011","unstructured":"Shaw LM. The insulin receptor substrate (IRS) proteins: at the intersection of metabolism and cancer. Cell Cycle. 2011;10(11):1750\u20136.","journal-title":"Cell Cycle"},{"issue":"12","key":"668_CR37","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1038\/nrc2536","volume":"8","author":"M Pollak","year":"2008","unstructured":"Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 2008;8(12):915\u201328.","journal-title":"Nat Rev Cancer"},{"issue":"8","key":"668_CR38","doi-asserted-by":"publisher","first-page":"5204","DOI":"10.1074\/jbc.M109.077818","volume":"285","author":"SA Whelan","year":"2010","unstructured":"Whelan SA, Dias WB, Thiruneelakantapillai L, Lane MD, Hart GW. Regulation of insulin receptor substrate 1 (IRS-1)\/AKT kinase-mediated insulin signaling by O-linked beta-N-acetylglucosamine in 3T3-L1 adipocytes. J Biol Chem. 2010;285(8):5204\u201311.","journal-title":"J Biol Chem"},{"issue":"35","key":"668_CR39","doi-asserted-by":"publisher","first-page":"14056","DOI":"10.1073\/pnas.0706517104","volume":"104","author":"F Tremblay","year":"2007","unstructured":"Tremblay F, Brule S, Hee Um S, Li Y, Masuda K, Roden M, et al. Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance. Proc Natl Acad Sci U S A. 2007;104(35):14056\u201361.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"668_CR40","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.yexcr.2016.10.006","volume":"349","author":"T Homma","year":"2016","unstructured":"Homma T, Fujii J. Heat stress promotes the down-regulation of IRE1alpha in cells: an atypical modulation of the UPR pathway. Exp Cell Res. 2016;349(1):128\u201338.","journal-title":"Exp Cell Res"},{"issue":"1","key":"668_CR41","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1750-2187-6-4","volume":"6","author":"A Shiryaev","year":"2011","unstructured":"Shiryaev A, Dumitriu G, Moens U. Distinct roles of MK2 and MK5 in cAMP\/PKA- and stress\/p38MAPK-induced heat shock protein 27 phosphorylation. J Mol Signal. 2011;6(1):4.","journal-title":"J Mol Signal"},{"issue":"2","key":"668_CR42","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/S0021-9258(18)48354-8","volume":"267","author":"J Landry","year":"1992","unstructured":"Landry J, Lambert H, Zhou M, Lavoie JN, Hickey E, Weber LA, et al. Human HSP27 is phosphorylated at serines 78 and 82 by heat shock and mitogen-activated kinases that recognize the same amino acid motif as S6 kinase II. J Biol Chem. 1992;267(2):794\u2013803.","journal-title":"J Biol Chem"},{"issue":"8","key":"668_CR43","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1158\/1535-7163.MCT-12-0072","volume":"11","author":"M Kumano","year":"2012","unstructured":"Kumano M, Furukawa J, Shiota M, Zardan A, Zhang F, Beraldi E, et al. Cotargeting stress-activated Hsp27 and autophagy as a combinatorial strategy to amplify endoplasmic reticular stress in prostate cancer. Mol Cancer Ther. 2012;11(8):1661\u201371.","journal-title":"Mol Cancer Ther"},{"key":"668_CR44","doi-asserted-by":"crossref","unstructured":"Okuno M, Adachi S, Kozawa O, Shimizu M and Yasuda I. The Clinical Significance of Phosphorylated Heat Shock Protein 27 (HSPB1) in Pancreatic Cancer. Int J Mol Sci. 2016;17(1).","DOI":"10.3390\/ijms17010137"},{"issue":"9","key":"668_CR45","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/nrclinonc.2011.71","volume":"8","author":"F Janku","year":"2011","unstructured":"Janku F, McConkey DJ, Hong DS, Kurzrock R. Autophagy as a target for anticancer therapy. Nat Rev Clin Oncol. 2011;8(9):528\u201339.","journal-title":"Nat Rev Clin Oncol"},{"issue":"3","key":"668_CR46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0122753","volume":"10","author":"P Li","year":"2015","unstructured":"Li P, Shi J, He Q, Hu Q, Wang YY, Zhang LJ, et al. Streptococcus pneumoniae induces autophagy through the inhibition of the PI3K-I\/Akt\/mTOR pathway and ROS hypergeneration in A549 cells. PLoS One. 2015;10(3):e0122753.","journal-title":"PLoS One"},{"issue":"20","key":"668_CR47","doi-asserted-by":"publisher","first-page":"9809","DOI":"10.1021\/jf902315e","volume":"57","author":"JY Hung","year":"2009","unstructured":"Hung JY, Hsu YL, Li CT, Ko YC, Ni WC, Huang MS, et al. 6-Shogaol, an active constituent of dietary ginger, induces autophagy by inhibiting the AKT\/mTOR pathway in human non-small cell lung cancer A549 cells. J Agric Food Chem. 2009;57(20):9809\u201316.","journal-title":"J Agric Food Chem"},{"key":"668_CR48","doi-asserted-by":"publisher","first-page":"192","DOI":"10.3389\/fcell.2019.00192","volume":"7","author":"K Schmeisser","year":"2019","unstructured":"Schmeisser K, Parker JA. Pleiotropic effects of mTOR and autophagy during development and aging. Front Cell Dev Biol. 2019;7:192.","journal-title":"Front Cell Dev Biol"},{"key":"668_CR49","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1478-811X-7-14","volume":"7","author":"K Mardilovich","year":"2009","unstructured":"Mardilovich K, Pankratz SL, Shaw LM. Expression and function of the insulin receptor substrate proteins in cancer. Cell Commun Signal. 2009;7:14.","journal-title":"Cell Commun Signal"},{"issue":"1","key":"668_CR50","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.biochi.2004.10.019","volume":"87","author":"P Gual","year":"2005","unstructured":"Gual P, Le Marchand-Brustel Y, Tanti JF. Positive and negative regulation of insulin signaling through IRS-1 phosphorylation. Biochimie. 2005;87(1):99\u2013109.","journal-title":"Biochimie."},{"issue":"5930","key":"668_CR51","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1126\/science.1160809","volume":"324","author":"MG Vander Heiden","year":"2009","unstructured":"Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029\u201333.","journal-title":"Science."},{"issue":"44","key":"668_CR52","doi-asserted-by":"publisher","first-page":"45304","DOI":"10.1074\/jbc.C400186200","volume":"279","author":"Y Li","year":"2004","unstructured":"Li Y, Soos TJ, Li X, Wu J, Degennaro M, Sun X, et al. Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser (1101). J Biol Chem. 2004;279(44):45304\u20137.","journal-title":"J Biol Chem"},{"issue":"10","key":"668_CR53","doi-asserted-by":"publisher","first-page":"8460","DOI":"10.1074\/jbc.M208518200","volume":"278","author":"KR Wick","year":"2003","unstructured":"Wick KR, Werner ED, Langlais P, Ramos FJ, Dong LQ, Shoelson SE, et al. Grb10 inhibits insulin-stimulated insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase\/Akt signaling pathway by disrupting the association of IRS-1\/IRS-2 with the insulin receptor. J Biol Chem. 2003;278(10):8460\u20137.","journal-title":"J Biol Chem"},{"key":"668_CR54","doi-asserted-by":"crossref","unstructured":"Choi SK, Kam H, Kim KY, Park SI and Lee YS. Targeting Heat Shock Protein 27 in Cancer: A Druggable Target for Cancer Treatment? Cancers (Basel). 2019;11(8).","DOI":"10.3390\/cancers11081195"},{"issue":"2","key":"668_CR55","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1023\/A:1006207009260","volume":"56","author":"RK Hansen","year":"1999","unstructured":"Hansen RK, Parra I, Lemieux P, Oesterreich S, Hilsenbeck SG, Fuqua SA. Hsp27 overexpression inhibits doxorubicin-induced apoptosis in human breast cancer cells. Breast Cancer Res Treat. 1999;56(2):187\u201396.","journal-title":"Breast Cancer Res Treat"},{"issue":"6","key":"668_CR56","doi-asserted-by":"publisher","first-page":"2380","DOI":"10.3892\/or.2014.3492","volume":"32","author":"MB Stope","year":"2014","unstructured":"Stope MB, Weiss M, Preuss M, Streitborger A, Ritter CA, Zimmermann U, et al. Immediate and transient phosphorylation of the heat shock protein 27 initiates chemoresistance in prostate cancer cells. Oncol Rep. 2014;32(6):2380\u20136.","journal-title":"Oncol Rep"},{"issue":"1","key":"668_CR57","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.bbrc.2005.08.273","volume":"337","author":"E Yasuda","year":"2005","unstructured":"Yasuda E, Kumada T, Takai S, Ishisaki A, Noda T, Matsushima-Nishiwaki R, et al. Attenuated phosphorylation of heat shock protein 27 correlates with tumor progression in patients with hepatocellular carcinoma. Biochem Biophys Res Commun. 2005;337(1):337\u201342.","journal-title":"Biochem Biophys Res Commun"},{"issue":"27","key":"668_CR58","doi-asserted-by":"publisher","first-page":"18852","DOI":"10.1074\/jbc.M801301200","volume":"283","author":"R Matsushima-Nishiwaki","year":"2008","unstructured":"Matsushima-Nishiwaki R, Takai S, Adachi S, Minamitani C, Yasuda E, Noda T, et al. Phosphorylated heat shock protein 27 represses growth of hepatocellular carcinoma via inhibition of extracellular signal-regulated kinase. J Biol Chem. 2008;283(27):18852\u201360.","journal-title":"J Biol Chem"},{"issue":"4","key":"668_CR59","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1016\/j.bbrc.2004.10.183","volume":"325","author":"Y Li","year":"2004","unstructured":"Li Y, Wang Y, Zhang C, Yuan W, Wang J, Zhu C, et al. ZNF322, a novel human C2H2 Kruppel-like zinc-finger protein, regulates transcriptional activation in MAPK signaling pathways. Biochem Biophys Res Commun. 2004;325(4):1383\u201392.","journal-title":"Biochem Biophys Res Commun"},{"key":"668_CR60","doi-asserted-by":"crossref","unstructured":"Ayuk SM and Abrahamse H. mTOR Signaling Pathway in Cancer Targets Photodynamic Therapy In Vitro. Cells. 2019;8(5).","DOI":"10.3390\/cells8050431"},{"issue":"4","key":"668_CR61","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.soc.2013.06.008","volume":"22","author":"B Hassan","year":"2013","unstructured":"Hassan B, Akcakanat A, Holder AM, Meric-Bernstam F. Targeting the PI3-kinase\/Akt\/mTOR signaling pathway. Surg Oncol Clin N Am. 2013;22(4):641\u201364.","journal-title":"Surg Oncol Clin N Am"},{"issue":"41","key":"668_CR62","doi-asserted-by":"publisher","first-page":"6723","DOI":"10.1038\/s41388-019-0928-x","volume":"38","author":"SY Liao","year":"2019","unstructured":"Liao SY, Kuo IY, Chen YT, Liao PC, Liu YF, Wu HY, et al. AKT-mediated phosphorylation enhances protein stability and transcription activity of ZNF322A to promote lung cancer progression. Oncogene. 2019;38(41):6723\u201336.","journal-title":"Oncogene."},{"issue":"17","key":"668_CR63","doi-asserted-by":"publisher","first-page":"5308","DOI":"10.1158\/1078-0432.CCR-07-5023","volume":"15","author":"E White","year":"2009","unstructured":"White E, DiPaola RS. The double-edged sword of autophagy modulation in cancer. Clin Cancer Res. 2009;15(17):5308\u201316.","journal-title":"Clin Cancer Res"},{"issue":"10","key":"668_CR64","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1038\/s41556-018-0201-5","volume":"20","author":"J Doherty","year":"2018","unstructured":"Doherty J, Baehrecke EH. Life, death and autophagy. Nat Cell Biol. 2018;20(10):1110\u20137.","journal-title":"Nat Cell Biol"},{"issue":"1","key":"668_CR65","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12929-016-0269-9","volume":"23","author":"J Jen","year":"2016","unstructured":"Jen J, Wang YC. Zinc finger proteins in cancer progression. J Biomed Sci. 2016;23(1):53.","journal-title":"J Biomed Sci"},{"issue":"8","key":"668_CR66","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1002\/ijc.28819","volume":"135","author":"KP Lai","year":"2014","unstructured":"Lai KP, Chen J, He M, Ching AK, Lau C, Lai PB, et al. Overexpression of ZFX confers self-renewal and chemoresistance properties in hepatocellular carcinoma. Int J Cancer. 2014;135(8):1790\u20139.","journal-title":"Int J Cancer"}],"container-title":["Journal of Biomedical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12929-020-00668-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12929-020-00668-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12929-020-00668-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T09:18:48Z","timestamp":1650532728000},"score":1,"resource":{"primary":{"URL":"https:\/\/jbiomedsci.biomedcentral.com\/articles\/10.1186\/s12929-020-00668-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,23]]},"references-count":66,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["668"],"URL":"https:\/\/doi.org\/10.1186\/s12929-020-00668-5","relation":{},"ISSN":["1423-0127"],"issn-type":[{"value":"1423-0127","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,23]]},"assertion":[{"value":"6 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 June 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing financial interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"75"}}